The HAS took the position that advanced therapies, which often target rare or serious illnesses without therapeutic alternative, deserve a specific treatment. First, because they are often authorized through an early marketing authorization on the basis of non-comparative studies on small patient samples. This data therefore does not match with data requirements in place for reimbursement. Second, because it is essential for patients to enable faster access to such innovative products.
This Plan proposes six priorities to anticipate, accelerate and accompany innovation. Advanced therapies should be prioritized in the reimbursement assessment. If the change of paradigm proves to be effective, this might result in a better assessment of advanced therapies.
1. Conditional opinions
For the assessment of the therapeutic value of medicinal products, the HAS has published a doctrine in 2018 to detail, harmonize and publish its assessment criteria.
A subsection was dedicated to the assessment in cases of high uncertainty. Although it did not prove to be impossible, it was limited to circumstances where reimbursement was indispensable to treat patients facing severe diseases with no therapeutic alternative.
In such circumstances, the HAS may issue an opinion but may require further clinical evidence as a condition of renewal, to be provided within five years.
Despite this mechanism, innovation was probably not properly accounted for in this case. For instance, in 2018, the HAS recognized only one major innovation (ASMR 1), seven moderate, 13 minor and 34 insufficient (ASMR 5). Yescarta and Kymriah, the first CAR-T cells assessed by the HAS, only received ASMR 3 and 4 levels, respectively.
The HAS therefore probably recognized that it was urgent to refurbish its toolbox to assess these advanced therapies.
Instead of issuing negative opinions on medicinal products for which there is insufficient data to establish therapeutic value, it proposes a true shift of evidence to post-MA.
New regulatory provisions should soon facilitate and broaden the scope of conditional opinions, in order to provide for anticipated reimbursement for advanced therapies. As a counterpart, the HAS will request and closely monitor additional data (particularly real-life data), that would be submitted online, and the reassessment period will be reduced from five to three years.
A key question will be the nature of post-MA data accepted by the HAS, as this is often where it reveals weaknesses in the reimbursement application files. The HAS states that it views phase IV studies as complementary to clinical trials. Interestingly, it points out that data which shall be collected under the ATU protocols would be a robust source of information. This is a positive signal towards the development of ATUs.
2. Early dialogues
In addition, the Plan also aims at promoting early dialogues, which have been created in 2010 and reinforced in 2016, to assist companies in the design of their study protocol, as this is an efficient way to ensure that relevant data is collected. A new guidance should be issued in a couple of months, and should create two assessment routes, and include patients in the pre-assessment phase.
No doubt that the HAS, which is at the forefront of the EUnetHTA initiative, as its vice president, will do its best to make it an efficient tool.
3. Fast track
Last but not least, the HAS invites companies to use more fast-track procedures. As a mirror to the procedures in place within the European Medicines Agency, the HAS commits to render its advice on reimbursement eligibility on an expedited basis by anticipating the formal assessment of an application for reimbursement. This may prove to be particularly useful for the assessment of these complex therapies. For the CAR-T cells, the HAS was able to issue its opinion within less than three months following the marketing authorization. But this is probably where the inconsistency lies: fast-tracking process are available to products which are presumed innovative because they (i) constitute new modalities for the management of diseases, (ii) are likely to bring clinically relevant progress by comparison with therapeutic alternatives and (iii) respond to poorly covered/unmet medical needs. It is thus surprising and disappointing that the HAS presumes such innovation, but ultimately grants an ASMR 3 or 4, which corresponds to moderate innovation.
It will be crucial to see whether the HAS will manage to recognize sufficient innovation with limited data. Otherwise, it will continue to assign rather low level innovation to advanced therapies, which will have a direct impact on their pricing, unless the pricing criteria themselves are changed to also take into account the peculiarities of these products. Moreover, one cannot exclude that the HAS may revise and increase the ASMR granted to a product on the basis of confirmatory post-MA data.
Finally, the HAS will inevitably face situations where confirmatory data is not provided in due time, or proves to be inaccurate. This should trigger the end of the reimbursement, but could create treatment breaches for induced patients.